When a person suffers from diabetes, the fasting blood glucose level exhibits 126 mg/dL or more. Even though the fasting blood glucose level falls within a normal range, there is a person exhibiting a postprandial blood glucose level as high as 140 to 200 mg/dL. Such a person is diagnosed as impaired glucose tolerance (hereinafter referred to as “IGT”). It has been considered that the risk of a cardiovascular disorder can be reduced by delaying onset of diabetes from IGT, and several supportive findings for this have been obtained. For example, the Da Qing IGT and Diabetes Study carried out in China in 1997 has reported that progression of IGT into Type II diabetes is significantly suppressed by diet and exercise (see Pan X R, et al., Diabets Care, vol 20, p. 534, 1997). As cases where medication is effective, when an α-glucosidase inhibitor, acarbose, which inhibits a hydrolysis of an oligosaccharide to delay glucose absorption from the small intestine, is administered, development of Type II diabetes from IGT is suppressed and further onset of hypertension is significantly suppressed. This is reported in the document (J.-L. Chiasson, et al., Lancent, vol. 359, p. 2072, 2002).
From the above, to suppress the onset of diabetes, it is important to control IGT by diet therapy, exercise therapy and medication.
Nevertheless, when a person suffers from diabetes, it comes to be necessary to control the blood glucose level at all times. Diabetes is basically treated by diet therapy and exercise therapy; however, when sufficient effect is not obtained by these therapies, medicament must be chosen.
On the small intestine epithelium of a mammal, a sodium dependent glucose cotransporter 1 (SGLT1) is expressed at a high frequency. It is known that SGLT1 serves depending upon sodium and plays a role in active transportation of glucose or galactose in the small intestine. Therefore, if glucose taken from a meal can be suppressed, IGT may be prevented or treated. Based on the concept, a pyrazole derivative inhibiting the activity of SGLT1 has been reported (see International Publication WO2002/098893, 2004/014932, 2004/018491, 2004/019958, 2005/121161 and 2004/050122).
Furthermore, a sodium dependent glucose cotransporter 2 (SGLT2) is expressed at a high frequency in the kidney. Glucose once filtrated by the glomerulus is reabsorbed via SGLT2 (see E. M. Wright, Am. J. Physiol. Renal. Physiol., vol. 280, p. F10, 2001). When an SGLT2 inhibitor is administered to a diabetic rat, glucose excretion into urine is facilitated, promoting a hypoglycemic action. From this, an SGLT2-specific inhibitor has been considered as a target molecule serving as a therapeutic agent for diabetes (see G. Toggenburger, et al. Biochem. Biophys. Acta., vol. 688, p. 557, 1982). In these circumstances, studies have been conducted on an SGLT2 inhibitor and various types of O-aryl glycoside derivatives have been provided (see EP Patent Application Publication No. 0850948A1 and International Publication WO2001/068660).
Accordingly, if the SGLT1 and SGLT2 activities can be simultaneously inhibited, a novel type of therapeutic agent for diabetes can be provided, which has not only a high postprandial glucose level suppression action ascribed to SGLT1 inhibition but also a progressive hypoglycemic action ascribed to SGLT2 inhibition.
Up to now, a C-phenyl glycoside derivative having a selective inhibitory activity to SGLT2 has been reported (see International Publication WO 2001/027128); however, a C-phenyl glycoside derivative strongly inhibiting both of SGLT1 and SGLT2 has not yet been reported.